Liquid chromatographs are commonly used for the separation of trace compounds to provide a degree of separation between the trace compound to be analyzed and the other compounds present in the mixture under investigation. The eluent from the liquid chromatograph, after the separation has occurred, is normally subjected to analysis to identify the trace compound or compounds of interest.
It is commonly desired to analyze the liquid from a liquid chromatograph in a mass analyzer such as a mass spectrometer. However, since mass spectrometers require an input in the form of free ions, it is usually necessary to evaporate the liquid from the liquid chromatograph, and to produce ions during or after the vaporization process.
One classical method which was commonly used was to spray the liquid from the liquid chromatograph onto a moving belt, which moves into a vacuum chamber where the belt was heated from below. The resultant vapor was then ionized by appropriate means. Another classical method was to spray large droplets from the liquid chromatograph into a heated ion source, so that the droplets were vaporized (typically by contact with the walls of the ion source and by exposure to the instrument vacuum). Both these methods use substantial heat, and this has severe disadvantages. The heat causes thermal decomposition of the compounds in question, and in addition, since the liquid from the liquid chromatograph often contains ammonium ions, these ions often cause ammonium chemical ionization to occur. The thermal decomposition and the ammonium chemical ionization create complexity in the final mass spectrum, making the analysis process more difficult.
More recently three alternative methods have been developed for introducing the liquid from a liquid chromatograph into a mass analyzer. In one method, referred to as ion evaporation, liquid is sprayed at atmospheric pressure into a chamber in front of the vacuum chamber orifice for the mass analyzer. The spray is directed across the orifice into a 90 degree elbow tube. This removes large droplets. The finer portion of the spray is removed less quickly, and since the small droplets therein carry a charge impressed by an electric field which is applied between the sprayer and an induction electrode, ions are released therefrom as the droplets evaporate. Such ions are driven toward the orifice by a deflector electrode. Although this method can accommodate relatively high flows (e.g. 1 milliliter per minute), the method is not particularly sensitive, partly because much of the sample is unused. Thus, the ion current from compounds of interest is very low in this method.
The second relatively modern method which has been developed is referred to as thermospray. In this method, the flow of liquid from the conventional liquid chromatograph passes through a capillary, the end of which is heated to between 200 and 350 degrees C. The resultant vaporization results in a spraying process, which is usually into a low pressure chamber but can be into an atmospheric pressure chamber. Contrary to the ion evaporation process, the droplets formed are charged not by an electric field, but rather by statistical fluctuations in the distribution of ions in solution when the liquid is dispersed into an aerosol. As the charged droplets evaporate, ions are released therefrom. Thermospray is relatively effective in producing a fine mist and currently is commonly used. However, a substantial disadvantage of the process is that again, some thermal decomposition occurs, even though not all of the liquid is directly subjected to heating. In addition, again some unwanted ammonium chemical ionization may occur. Therefore, while the temperatures used can be carefully controlled by a microprocessor, nevertheless, thermospray is commonly recognized as being a "fussy" process which may give good results one day and poor results another. In addition, in practice some workers report that thermospray is generally less sensitive for ionic compounds (i.e. compounds which form ions in solution) than is the ion spray technique.
The third process which has been used to produce ions from the liquid of a small-bore liquid chromatograph, and to introduce such ions into a mass analyzer, is the so-called electrospray technique. In this technique, liquid from the liquid chromatograph is directed through a capillary tube the end of which is connected to one pole of a high voltage source. The end of the capillary tube is spaced from the orifice plate through which ions travel into the mass analyzer vacuum chamber. The orifice plate is connected to the other pole of the high voltage source. The electric field generates charged droplets, producing an induced liquid flow in the capillary without a pump, and the droplets evaporate to produce ions. Electrospray can be carried out without a pump (in which case the flow is 1 to 2 microliters per minute) or with a pump.
The electrospray method has several disadvantages. Firstly, it can handle only a very small flow, typically only up to about 10 microliters per minute. Faster pumping produces larger droplets, causing the ion signal to fall off and also to become unstable. Secondly, the high voltages needed to disperse a larger liquid flow into fine droplets tend to create an electrical or corona discharge. The discharge adds complexity to the spectrum produced by the mass analyzer, causing difficulties in interpretation, and in addition, for unknown reasons, it tends to suppress the ion signal from the evaporated droplets. A further disadvantage is that the electrospray method is very sensitive to the position of the end of the capillary tube relative to the orifice plate.
In addition, the electrospray method requires that the proportion of water in the liquid be low, since otherwise a stream of large droplets tends to be produced. The large droplets reduce the sensitivity (i.e. the ion signal) and also affect the stability of the ion signal, i.e. large fluctuations occur in the ion signal.
Prior Electrospray (ES) apparatus and ion spray (IS) apparatus and methods of interfacing liquid chromatographs with a mass analyzer including U.S. Pat. No. 4,861,988 relating to "Ion Spray Apparatus and Method" are deficient in the amount of liquid that can be accommodated in the interface without loss of sensitivity and selectivity. Prior art Electrospray interfaces only accommodate liquid flow rates of from about 1.0 to 10 .mu.L per minute. It would be advantageous to have interfaces that would operate with high sensitivity at flow rates of from 100 .mu.L up to 1000 .mu.L-2000 .mu.L/minute. Known Electrospray and Ion Spray interfaces suffer also from the fact that they produce a high abundance of multiply charged ions which detract from the identification of unknown chemicals by their mass spectra. It would be further advantageous to have an interface that predominately generates singly charged ions.
The present invention resolves the various deficiencies of the prior art interfaces.